Age-related differences in the use of guideline-recommended medical and interventional therapies for acute coronary syndromes: a cohort study.

OBJECTIVES: To compare the use of guideline-recommended medical and interventional therapies in older and younger patients with acute coronary syndromes (ACSs). DESIGN: Prospective cohort study. SETTING: Fifty-five hospitals in Switzerland. PARTICIPANTS: Eleven thousand nine hundred thirty-two patients with ACS enrolled between March 1, 2001, and June 30, 2006. ACS definition included ST-segment elevation myocardial infarction (STEMI), non-ST-segment elevation myocardial infarction (NSTEMI), and unstable angina pectoris (UA). MEASUREMENTS: Use of medical and interventional therapies was determined after exclusion of patients with contraindications and after adjustment for comorbidities. Multivariate logistic regression models were used to calculate odds ratios (ORs) per year increase in age. RESULTS: Elderly patients were less likely to receive acetylsalicylic acid (OR=0.976, 95% confidence interval (CI)=0.969-0.980) or beta-blockers (OR=0.985, 95% CI=0.981-0.989). No age-dependent difference was found for heparin use. Elderly patients with STEMI were less likely to receive percutaneous coronary intervention (PCI) or thrombolysis (OR=0.955, 95% CI=0.949-0.961). Elderly patients with NSTEMI or UA less often underwent PCI (OR=0.943, 95% CI=0.937-0.949). CONCLUSION: Elderly patients across the whole spectrum of ACS were less likely to receive guideline-recommended therapies, even after adequate adjustment for comorbidities. Prognosis of elderly patients with ACS may be improved by increasing adherence to guideline-recommended medical and interventional therapies.

A critical review of the molecular pathophysiology of lenalidomide sensitivity in 5q - myelodysplastic syndromes.

Abstract The 5q deletion is a chromosomal abnormality that is observed in a subset of myelodysplastic syndromes (MDS). When isolated, this abnormality defines a specific clinical syndrome termed MDS associated with isolated deletion 5q, presenting with macrocytic anemia, normal platelet count or slight thrombocytosis, hypolobated megakaryocytes and fewer than 5% blasts in the bone marrow. MDS with the 5q deletion have a particular sensitivity to treatment with lenalidomide, a thalidomide analog. In this article, molecular changes in 5q- MDS derived from haploinsufficiency of genes encoded from the deleted region in 5q are reviewed, and mechanisms that link these molecular lesions with lenalidomide sensitivity are proposed.

Un projet multicentrique suisse pour améliorer la prévention et la récidive après un syndrome coronarien aigu [A Swiss multicentric project to improve the prevention of cardiovascular event recurrence after acute coronary syndromes].

Recurrence of cardiovascular events and mortality remain high after acute coronary syndromes. A Swiss multicentric study, "Inflammation and acute coronary syndromes (ACS)--Novel strategies for prevention and clinical managements", is currently underway with the support of the Swiss National Science Foundation. The study includes a clinical research subproject of which the aim is to assess the impact of the ELIPS program (multi-dimEnsionaL prevention Program after acute coronary Syndrome) on the recurrence of cardiovascular events after an ACS. The basic research sub-projects aim to investigate novel cardiovascular risk biomarkers and genetic determinants of recurrence and to study the role of stem cells after an ACS. Another sub-project will evaluate intracoronary imaging techniques and the efficacy of different types of stents.

Syndromes néoplasiques héréditaires avec atteinte cutanée [Cutaneous lesions in genetic tumor syndromes]

Genetic tumor syndromes reflect an inherited predisposition to develop benign and malignant tumors. Increased frequency of neoplasms within the family or occurring at an early age are clinical clues for a possible underlying genetic susceptibility. Awareness of their associated cutaneous manifestations can facilitate early detection of risk for tumors. The goal of this article is to review clinical and molecular features of some genetic tumor syndrome which present with skin involvement at birth or during childhood.

Comment dépister les syndromes gériatriques au cabinet [How to screen geriatric conditions in primary care?].

The ongoing aging of the population will lead to an increasing prevalence of chronic diseases and functional limitation. Preventative measures need to be promoted to prevent health care utilization and health costs explosion. Among these measures, those aimed at promoting early recognition of chronic conditions associated with functional decline, will have to be reinforced. This paper proposes simple, feasible, and efficient procedures to screen, in primary care practices, common geriatric conditions, as cognitive impairment, gait impairment, hearing and vision impairment or functional limitation.

Serum androgen levels in elite female athletes.

OBJECTIVE: Prior to the implementation of the blood steroidal module of the Athlete Biological Passport, we measured the serum androgen levels among a large population of high-level female athletes as well as the prevalence of biochemical hyperandrogenism and some disorders of sex development (DSD). METHODS AND RESULTS: In 849 elite female athletes, serum T, dehydroepiandrosterone sulphate, androstenedione, SHBG, and gonadotrophins were measured by liquid chromatography-mass spectrometry high resolution or immunoassay. Free T was calculated. The sampling hour, age, and type of athletic event only had a small influence on T concentration, whereas ethnicity had not. Among the 85.5% that did not use oral contraceptives, 168 of 717 athletes were oligo- or amenorrhoic. The oral contraceptive users showed the lowest serum androgen and gonadotrophin and the highest SHBG concentrations. After having removed five doped athletes and five DSD women from our population, median T and free T values were close to those reported in sedentary young women. The 99th percentile for T concentration was calculated at 3.08 nmol/L, which is below the 10 nmol/L threshold used for competition eligibility of hyperandrogenic women with normal androgen sensitivity. Prevalence of hyperandrogenic 46 XY DSD in our athletic population is approximately 7 per 1000, which is 140 times higher than expected in the general population. CONCLUSION: This is the first study to establish normative serum androgens values in elite female athletes, while taking into account the possible influence of menstrual status, oral contraceptive use, type of athletic event, and ethnicity. These findings should help to develop the blood steroidal module of the Athlete Biological Passport and to refine more evidence-based fair policies and recommendations concerning hyperandrogenism in female athletes.

CD34/QBEND10 immunostaining in bone marrow biopsies: an additional parameter for the diagnosis and classification of myelodysplastic syndromes.

CD34/QBEND10 immunostaining has been assessed in 150 bone marrow biopsies (BMB) including 91 myelodysplastic syndromes (MDS), 16 MDS-related AML, 25 reactive BMB, and 18 cases where RA could neither be established nor ruled out. All cases were reviewed and classified according to the clinical and morphological FAB criteria. The percentage of CD34-positive (CD34 +) hematopoietic cells and the number of clusters of CD34+ cells in 10 HPF were determined. In most cases the CD34+ cell count was similar to the blast percentage determined morphologically. In RA, however, not only typical blasts but also less immature hemopoietic cells lying morphologically between blasts and promyelocytes were stained with CD34. The CD34+ cell count and cluster values were significantly higher in RA than in BMB with reactive changes (p<0.0001 for both), in RAEB than in RA (p=0.0006 and p=0.0189, respectively), in RAEBt than in RAEB (p=0.0001 and p=0.0038), and in MDS-AML than in RAEBt (p<0.0001 and p=0.0007). Presence of CD34+ cell clusters in RA correlated with increased risk of progression of the disease. We conclude that CD34 immunostaining in BMB is a useful tool for distinguishing RA from other anemias, assessing blast percentage in MDS cases, classifying them according to FAB, and following their evolution.

Syndromes auto-inflammatoires en dermatologie [Autoinflammatory syndromes in dermatology].

Hereditary periodic fever syndromes, also called autoinflammatory syndromes, are characterized by relapsing fever and additional manifestations such as skin rashes, mucosal manifestations, or arthralgias. Some of these disorders present without fever but with the associated systemic manifestations. The responsible mutated genes have been identified for most of these disorders, which lead to the induction of the uncontrolled and excessive production of interleukin-1beta (IL-1beta). The inhibition of IL-1beta through IL-1 receptor antagonist or monoclonal antibody against IL-1beta is used with success in most of these diseases. In case of TNF-receptor associated periodic syndrome (TRAPS) and paediatric granulomatous arthritis (PGA), TNF-antagonists may also be used; in familial Mediterranean fever (FMF) colchicine remains the first choice.

First and second branchial arch syndromes: multimodality approach.

First and second branchial arch syndromes (BAS) manifest as combined tissue deficiencies and hypoplasias of the face, external ear, middle ear and maxillary and mandibular arches. They represent the second most common craniofacial malformation after cleft lip and palate. Extended knowledge of the embryology and anatomy of each branchial arch derivative is mandatory for the diagnosis and grading of different BAS lesions and in the follow-up of postoperative patients. In recent years, many new complex surgical approaches and procedures have been designed by maxillofacial surgeons to treat extensive maxillary, mandibular and external and internal ear deformations. The purpose of this review is to evaluate the role of different imaging modalities (orthopantomogram (OPG), lateral and posteroanterior cephalometric radiographs, CT and MRI) in the diagnosis of a wide spectrum of first and second BAS, including hemifacial microsomia, mandibulofacial dysostosis, branchio-oto-renal syndrome, Pierre Robin sequence and Nager acrofacial dysostosis. Additionally, we aim to emphasize the importance of the systematic use of a multimodality imaging approach to facilitate the precise grading of these syndromes, as well as the preoperative planning of different reconstructive surgical procedures and their follow-up during treatment.

External irradiation with or without long-term androgen suppression for prostate cancer with high metastatic risk: 10-year results of an EORTC randomised study.

BACKGROUND: We did a randomised phase 3 trial assessing the benefit of addition of long-term androgen suppression with a luteinising-hormone-releasing hormone (LHRH) agonist to external irradiation in patients with prostate cancer with high metastatic risk. In this report, we present the 10-year results. METHODS: For this open-label randomised trial, eligible patients were younger than 80 years and had newly diagnosed histologically proven T1-2 prostatic adenocarcinoma with WHO histological grade 3 or T3-4 prostatic adenocarcinoma of any histological grade, and a WHO performance status of 0-2. Patients were randomly assigned (1:1) to receive radiotherapy alone or radiotherapy plus immediate androgen suppression. Treatment allocation was open label and used a minimisation algorithm with institution, clinical stage of the disease, results of pelvic-lymph-node dissection, and irradiation fields extension as minimisation factors. Patients were irradiated externally, once a day, 5 days a week, for 7 weeks to a total dose of 50 Gy to the whole pelvis, with an additional 20 Gy to the prostate and seminal vesicles. The LHRH agonist, goserelin acetate (3·6 mg subcutaneously every 4 weeks), was started on the first day of irradiation and continued for 3 years; cyproterone acetate (50 mg orally three times a day) was given for 1 month starting a week before the first goserelin injection. The primary endpoint was clinical disease-free survival. Analysis was by intention to treat. The trial is registered at ClinicalTrials.gov, number NCT00849082. FINDINGS: Between May 22, 1987, and Oct 31, 1995, 415 patients were randomly assigned to treatment groups and were included in the analysis (208 radiotherapy alone, 207 combined treatment). Median follow-up was 9·1 years (IQR 5·1-12·6). 10-year clinical disease-free survival was 22·7% (95% CI 16·3-29·7) in the radiotherapy-alone group and 47·7% (39·0-56·0) in the combined treatment group (hazard ratio [HR] 0·42, 95% CI 0·33-0·55, p<0·0001). 10-year overall survival was 39·8% (95% CI 31·9-47·5) in patients receiving radiotherapy alone and 58·1% (49·2-66·0) in those allocated combined treatment (HR 0·60, 95% CI 0·45-0·80, p=0·0004), and 10-year prostate-cancer mortality was 30·4% (95% CI 23·2-37·5) and 10·3% (5·1-15·4), respectively (HR 0·38, 95% CI 0·24-0·60, p<0·0001). No significant difference in cardiovascular mortality was noted between treatment groups both in patients who had cardiovascular problems at study entry (eight of 53 patients in the combined treatment group had a cardiovascular-related cause of death vs 11 of 63 in the radiotherapy group; p=0·60) and in those who did not (14 of 154 vs six of 145; p=0·25). Two fractures were reported in patients allocated combined treatment. INTERPRETATION: In patients with prostate cancer with high metastatic risk, immediate androgen suppression with an LHRH agonist given during and for 3 years after external irradiation improves 10-year disease-free and overall survival without increasing late cardiovascular toxicity.

Indications à la coronarographie en urgence. Partie II: syndromes coronariens aigus sans élévation du segment ST [Indications for urgent coronary angiography. Part II: Acute coronary syndromes without ST-segment elevation]

The optimal treatment strategy for patients presenting with an acute coronary syndrome without ST elevation is controversial and different therapeutic approaches are recognized. Currently, given the literature available, it is not possible to recommend a universal systematic invasive approach. It is essential to individually risk stratify patients in order to identify those high risk patients that have been shown to benefit from an invasive strategy. Compared to conservative medical treatment, patients at low risk have not been shown to benefit from an invasive strategy. Urgent coronary angiography remains recommended for those patients with persistent or recurrent ischemic symptoms under optimal medical treatment.

Prevalence of Acute Coronary Syndrome in Patients Suspected for Pulmonary Embolism or Acute Aortic Syndromes: Rational for "Double" and "Triple" Rule-Out Concepts

PURPOSE To evaluate the prevalence of acute coronary syndrome (ACS) in patients presenting initially with atypical chest pain and suspected to have pulmonary embolism (PE) or acute aortic syndromes (AAS). To evaluate the overlap between ACS, PE and AAS in routine practice and determine how many patients could have benefit from a single CT protocol to rule out ACS at the same time as PE and AAS. METHOD AND MATERIALS Our electronic hospital database revealed 1122 consecutive patients who underwent a thoracic CT angiography for PE or AAS from 2004 to 2006 (mean age, 63±13 years). Patients without chest pain were excluded from this study. Thus, 447 patients presented with isolated atypical chest were included in the analysis. All patients who underwent a thoracic CT scan previously received standard clinical care and were initially considered as non ACS. The final diagnosis was obtained by the hospital stay report. RESULTS Among the 447 patients with atypical chest pain, 25 (5.5%) were finally found to have ACS: 19 patients (4.2%) were suspected for PE and 6 (1. 3%) were suspected for AAS. There were 90 patients diagnosed to have PE, 89 (98.8%) of them were suspected for PE while only 1 (1%) was suspected for AAS. Eleven patients diagnosed to have AAS, 9 (82%) of them were suspected for AAS while 2 (18%) were suspected for PE. CONCLUSION In clinical practice, the overlap between PE, AAS and ACS is limited which make the triple rule-out studies less recommended to be done at the time being because of the high dose radiation. A double rule-out investigation is suggested to be done for patients being evaluated for atypical chest pain and suspected of having AAS or PE because of a significant overlap between the two entities as well it doesn't implicate any increment in radiation dose. CLINICAL RELEVANCE/APPLICATION With 64-slice CT, coronary circulation and total chest can be evaluated at the same time offering new opportunitie for the evaluation of three major life-threatening conditions :ACS,PE and AAS.

BCOR analysis in patients with OFCD and Lenz microphthalmia syndromes, mental retardation with ocular anomalies, and cardiac laterality defects.

Oculofaciocardiodental (OFCD) and Lenz microphthalmia syndromes form part of a spectrum of X-linked microphthalmia disorders characterized by ocular, dental, cardiac and skeletal anomalies and mental retardation. The two syndromes are allelic, caused by mutations in the BCL-6 corepressor gene (BCOR). To extend the series of phenotypes associated with pathogenic mutations in BCOR, we sequenced the BCOR gene in patients with (1) OFCD syndrome, (2) putative X-linked ('Lenz') microphthalmia syndrome, (3) isolated ocular defects and (4) laterality phenotypes. We present a new cohort of females with OFCD syndrome and null mutations in BCOR, supporting the hypothesis that BCOR is the sole molecular cause of this syndrome. We identify for the first time mosaic BCOR mutations in two females with OFCD syndrome and one apparently asymptomatic female. We present a female diagnosed with isolated ocular defects and identify minor features of OFCD syndrome, suggesting that OFCD syndrome may be mild and underdiagnosed. We have sequenced a cohort of males diagnosed with putative X-linked microphthalmia and found a mutation, p.P85L, in a single case, suggesting that BCOR mutations are not a major cause of X-linked microphthalmia in males. The absence of BCOR mutations in a panel of patients with non-specific laterality defects suggests that mutations in BCOR are not a major cause of isolated heart and laterality defects. Phenotypic analysis of OFCD and Lenz microphthalmia syndromes shows that in addition to the standard diagnostic criteria of congenital cataract, microphthalmia and radiculomegaly, patients should be examined for skeletal defects, particularly radioulnar synostosis, and cardiac/laterality defects.